Myeloid cell surface antigen CD33 (CD33) (CD33)

CD33, also known as Siglec-3, is a 67 kDa transmembrane glycoprotein and a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family [2, 4]. It is predominantly expressed on the surface of myeloid lineage cells, including myeloid progenitors, monocytes, and granulocytes, as well as on the leukemic blasts of approximately 85-90% of patients with acute myeloid leukemia (AML) [1, 11, 13]. Biologically, CD33 functions as an inhibitory receptor; upon binding to sialic acid ligands, its intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) are phosphorylated, recruiting phosphatases like SHP-1 and SHP-2 to dampen immune cell activation and phagocytosis [2, 4, 6]. In the context of oncology, CD33 is a validated therapeutic target, most notably for the antibody-drug conjugate gemtuzumab ozogamicin, which delivers a potent cytotoxic payload directly to malignant cells [5, 11, 12]. Beyond AML, CD33 is implicated in the pathogenesis of Alzheimer's disease, where certain genetic variants influence the ability of microglia to clear amyloid-beta plaques [4, 7]. Therapeutic strategies targeting CD33 include ADCs, bispecific antibodies, and CAR-T cell therapies, though challenges such as slow internalization and potential liver toxicity, specifically veno-occlusive disease, remain significant clinical considerations [8, 11, 12].

Other names

Siglec-3Sialic acid-binding Ig-like lectin 3SIGLEC3gp67p67

Antibody-drug conjugates (ADCs) bind to CD33 and are internalized to release cytotoxic agents like calicheamicin, inducing DNA damage and apoptosis [2, 5, 11, 12]. Bispecific T-cell engagers (BiTEs) and CAR-T cells redirect T-cells to recognize and kill CD33-expressing leukemic cells [5, 8].